Biosensing platforms based on localized surface plasmon resonance (LSPR) or surface enhanced Raman scattering (SERS) hold enormous potential to provide highly sensitive, cost-effective, and point-of-care diagnostic tools. However, similar to many other analytical methodologies such as enzyme-linked immunosorbent assays (ELISAs), present plasmonic biosensors use natural antibodies. The use of natural antibodies in analytical methods is ubiquitous, with applications in disease diagnosis, toxicology testing, and biotechnology. Natural antibody production is expensive and time consuming. Both the time and expense required for natural antibody production and their poor stability constitute a barrier to the rapid development and widespread application of plasmonic biosensors and clinical protocols for disease-specific screening.
Although gold nanoparticles may enable LSPR spectroscopy and improve sensitivity, they have so far been used as a layer underneath or on top of a molecularly imprinted polymer (MIP) film. In these configurations, nanoparticles are not used as direct transduction elements but for enhancing Raman scattering from analyte molecules (SERS) or propagating surface plasmon resonance (SPR) on planar gold surfaces. Other reported techniques involve embedding gold nanoparticles in a molecularly imprinted polymer or so-called Au-MIP nanocomposites, which results in a random distribution of the nanoparticles and the molecular imprints. Biomacromolecular imprinting of noble-metal nanoparticles that takes full advantage of the unique structural and localized plasmonic properties of each individual nanoparticle continues to be a serious challenge. Present metal nanostructures have low refractive index sensitivity, which can impede detection of biomolecules at low concentrations.
Most of the existing plasmonic sensors rely on natural antibodies for the capture of target biomolecules (e.g., disease biomarkers). However, natural antibodies suffer from numerous shortcomings such as poor chemical stability, excessive cost and limited shelf-life. Moreover, they pose a significant challenge in efficient integration with abiotic micro- and nanotransduction platforms.
Accordingly, there is a need for structures with a higher refractive index sensitivity for plasmonic biosensing. In addition, there is a need for a sensor with improved chemical stability, increased shelf-life, and more efficient integration with abiotic platforms.